Functionalized magnetic hydrogel encapsulation of human dental follicle stem cells under a static magnetic field...

Repairing large-scale craniomaxillofacial bone defects is hindered by a limited availability of stem-cell sources and a low osteogenic efficiency. To address these challenges, Fe₃O₄ nanoparticles were modified with methacrylic anhydride (MAA), which helped to introduce photopolymerizable methacryloyl groups, resulting in MAA-Fe₃O₄ nanoparticles that exhibit excellent magnetic properties and colloidal stability. These nanoparticles were incorporated into gelatin methacryloyl (GelMA) and covalently crosslinked to form an injectable, photocurable GelMA-Fe₃O₄ magnetic composite hydrogel. This hydrogel provided a three-dimensional culture microenvironment for human dental follicle stem cells (hDFSCs), and upon encapsulation, osteogenesis was significantly enhanced under a 100 mT static magnetic field (SMF). In vitro, GelMA-Fe₃O₄ hydrogels demonstrated increased porosity and improved mechanical properties, thereby significantly promoting hDFSCs proliferation, adhesion and spreading. Additionally, under SMF exposure, the expression of osteogenesis-related genes and proteins, including alkaline phosphatase (ALP), Runx2, Col-I and OPN, was significantly upregulated. In a rat calvarial defect model, bone mineralization centers with multi-site distribution were observed in the GelMA-Fe₃O₄ + SMF group as early as 4 weeks postoperatively, leading to high-quality defect repair. The limitations of traditional 'peripheral-to-center' unidirectional repair were overcome by this model of synchronous multi-site osteogenesis, maximizing bone regeneration with a minimal number of stem cells and providing an efficient, controllable tissue-engineering strategy for the clinical treatment of craniomaxillofacial bone defects.